EP2603309A1 - Vorrichtung und verfahren zum testen von hohlfasermembranfiltern - Google Patents
Vorrichtung und verfahren zum testen von hohlfasermembranfilternInfo
- Publication number
- EP2603309A1 EP2603309A1 EP11741239.5A EP11741239A EP2603309A1 EP 2603309 A1 EP2603309 A1 EP 2603309A1 EP 11741239 A EP11741239 A EP 11741239A EP 2603309 A1 EP2603309 A1 EP 2603309A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- filter
- membrane
- testing liquid
- pressure
- testing
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 239000012528 membrane Substances 0.000 title claims abstract description 150
- 238000012360 testing method Methods 0.000 title claims abstract description 95
- 238000000034 method Methods 0.000 title claims abstract description 45
- 239000000835 fiber Substances 0.000 title claims abstract description 28
- 239000007788 liquid Substances 0.000 claims abstract description 93
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 22
- 239000012530 fluid Substances 0.000 claims description 21
- 239000012510 hollow fiber Substances 0.000 claims description 13
- 238000012544 monitoring process Methods 0.000 claims description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 4
- 229930195733 hydrocarbon Natural products 0.000 claims description 2
- 150000002430 hydrocarbons Chemical class 0.000 claims description 2
- 239000000203 mixture Substances 0.000 claims description 2
- 229920000136 polysorbate Polymers 0.000 claims description 2
- 229920002545 silicone oil Polymers 0.000 claims description 2
- 239000004215 Carbon black (E152) Substances 0.000 claims 1
- 235000008733 Citrus aurantifolia Nutrition 0.000 abstract 1
- 235000011941 Tilia x europaea Nutrition 0.000 abstract 1
- 239000004571 lime Substances 0.000 abstract 1
- 210000004379 membrane Anatomy 0.000 description 129
- 239000008280 blood Substances 0.000 description 27
- 210000004369 blood Anatomy 0.000 description 27
- 239000011148 porous material Substances 0.000 description 24
- 238000011282 treatment Methods 0.000 description 8
- 238000000502 dialysis Methods 0.000 description 7
- 238000009792 diffusion process Methods 0.000 description 5
- 230000035699 permeability Effects 0.000 description 5
- 238000000108 ultra-filtration Methods 0.000 description 5
- 230000002950 deficient Effects 0.000 description 4
- -1 e.g. Substances 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 238000001631 haemodialysis Methods 0.000 description 3
- 230000000322 hemodialysis Effects 0.000 description 3
- 230000002209 hydrophobic effect Effects 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 3
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 3
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 3
- 238000013022 venting Methods 0.000 description 3
- 101100284769 Drosophila melanogaster hemo gene Proteins 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 244000052616 bacterial pathogen Species 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000000385 dialysis solution Substances 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000011049 filling Methods 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 238000007789 sealing Methods 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 238000012795 verification Methods 0.000 description 2
- 238000009736 wetting Methods 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 239000002033 PVDF binder Substances 0.000 description 1
- 239000004695 Polyether sulfone Substances 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 238000009530 blood pressure measurement Methods 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000000919 ceramic Substances 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 238000002615 hemofiltration Methods 0.000 description 1
- 229920001477 hydrophilic polymer Polymers 0.000 description 1
- 229920001600 hydrophobic polymer Polymers 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 229910010272 inorganic material Inorganic materials 0.000 description 1
- 239000011147 inorganic material Substances 0.000 description 1
- 238000009434 installation Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 239000011368 organic material Substances 0.000 description 1
- 239000012466 permeate Substances 0.000 description 1
- 229920002492 poly(sulfone) Polymers 0.000 description 1
- 229920006393 polyether sulfone Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 229920001343 polytetrafluoroethylene Polymers 0.000 description 1
- 239000004810 polytetrafluoroethylene Substances 0.000 description 1
- 229920002981 polyvinylidene fluoride Polymers 0.000 description 1
- 238000001223 reverse osmosis Methods 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 229920001059 synthetic polymer Polymers 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
- G01N15/08—Investigating permeability, pore-volume, or surface area of porous materials
- G01N15/082—Investigating permeability by forcing a fluid through a sample
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D65/00—Accessories or auxiliary operations, in general, for separation processes or apparatus using semi-permeable membranes
- B01D65/10—Testing of membranes or membrane apparatus; Detecting or repairing leaks
- B01D65/102—Detection of leaks in membranes
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D2313/00—Details relating to membrane modules or apparatus
- B01D2313/10—Specific supply elements
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
- G01N15/08—Investigating permeability, pore-volume, or surface area of porous materials
- G01N15/082—Investigating permeability by forcing a fluid through a sample
- G01N15/0826—Investigating permeability by forcing a fluid through a sample and measuring fluid flow rate, i.e. permeation rate or pressure change
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N15/00—Investigating characteristics of particles; Investigating permeability, pore-volume or surface-area of porous materials
- G01N15/08—Investigating permeability, pore-volume, or surface area of porous materials
- G01N2015/084—Testing filters
Definitions
- the present disclosure relates to a device and a process for testing filters.
- the invention can be usefully applied for filters of an apparatus for extracorporeal blood treatment, for instance, membrane filters normally used in a device for on-line preparation of a dialysis liquid and/or a re ⁇ placement liquid, in the ambit of an apparatus for hemo- dialysis and/or hemo (dia) filtration, or filters used for hemodialysis and/or hemo (dia) filtration .
- Diffusion and/or filtration devices comprising hollow fiber membranes are used in various medical treatments which remove unwanted substances from body fluids, e.g., blood. Examples of such treatments are hemodialysis, hemodiafiltration and hemofiltration .
- Membrane filters are also used in the production of sterile liquids, by causing the liquid to pass through a semi-permeable mem ⁇ brane able to filter the germs.
- Various processes for checking the integrity of a filter have been described.
- One of the known processes is the bubble point test
- BPT BPT
- the test briefly comprises the following stages: the membrane is wetted so that the pores are full of liquid; a first side of the membrane is connected to a gas source, while the opposite side is connected to a liquid for easy detection of gas bubbles; the first side of the membrane is gradually pressurized with the gas; while the gas pressure on the first side remains rela ⁇ tively low, a modest amount of gas will displace, by dif ⁇ fusion, through the liquid contained in the membrane pores towards the second side of the membrane; this amount of gas flow is proportional to the speed of in ⁇ crease of gas pressure on the first side; when the gas pressure reaches a certain level, the liquid contained in the largest pores is forced to exit from the pores them- selves, and a considerable amount of gas crosses the largest pores, reaching the liquid connected to the sec ⁇
- US-A 5,064,529 describes an automatic BPT (without the need to observe the moment of gas bubble formation) to check whether the effective BP pressure of the membrane corresponds to the desired BP pressure corresponding to the maximum diameter of the pores indicated by the mem ⁇ brane manufacturer; in a first stage the first side of the membrane is pressurized with the gas at a predeter- mined constant pressurization speed, at the end of which first stage the pressure measured on the first side of the membrane should correspond to a predetermined theo ⁇ retical pressure; the pressurization speed and the pres- surization time are chosen so that the above-mentioned theoretical pressure is lower than the desired BP pres ⁇ sure; if the pressure measured after the predetermined time does not correspond to the theoretical pressure, a fault is signaled due, probably, to the breakage of the membrane or a faulty installation of the filter; in a second stage, the pressurization is halted for a certain time period in which the pressure should remain substan ⁇ tially constant; if,
- US 5,594,161 describes a process for testing the integ ⁇ rity of one or more filtering elements in which the inlet side of the filter element is wetted and subjected to a gas pressure which is kept constant, while the pressure is measured on the outlet side which, previously, has been made part of a closed system. If, after a predetermined time, the outlet pressure does not exceed a prede ⁇ termined threshold value, the filter element is consid ⁇ ered intact.
- US-A 4,614,109 describes a process for checking the permeability of a wet membrane of a filter, based both on a search for the BP pressure and on the determination of the gas diffusion before reaching BP pressure.
- the filter membrane is first impregnated with liquid; thereafter, the inlet side of the membrane is gradually pressurized by introduction of a gas; the gas that passes by diffusion through the membrane is col ⁇ lected in a graduated container; the permeability of the membrane is calculated on the basis of the trans-membrane pressure measured on the two sides o the membrane, and of the quantity of gas diffused through the membrane per unit of time using the graduated container.
- the visual bubble point because it can be visually detected
- the production of gas bubbles on the exit side of the membrane sharply increases: this, as mentioned above, is due to the fact that, on reaching the bubble point pres ⁇ sure, the passage of gas through the membrane occurs both by diffusion (in a small part) and (prevalently) by ef ⁇ fect of the formation of gas conduits through the pores of the membrane.
- US-A 6,228,271 describes a process for testing the integ- rity of filter membranes in which the filter inlet chamber is emptied of liquid and filled with air at atmos ⁇ pheric pressure, while the outlet chamber remains full of liquid.
- a depression is then created in the outlet cham ⁇ ber in order to create a trans-membrane pressure; after the depression has been stabilized, for example at a value comprised between 0.2 and 0.9 bar (absolute pres ⁇ sure) , and before completely evacuating the liquid from the outlet chamber, the constant flow of liquid is meas ⁇ ured as it exits the outlet chamber, which corresponds to the air flow passing through the perforations of the membrane; the integrity of the membrane is thus measured on the basis of the value measured for the liquid flow.
- a typical sealed pressure test involves, for ex- ample, a side of the membrane being brought up to a pre ⁇ determined gas pressure, below BP pressure, comprised in the diffusion range, i.e. a range in which the pressure in the second membrane chamber increases proportionally to the pressure in the first side; when the pressure has been reached, the gas supply is interrupted and the pres ⁇ sure on the first side monitored; if the drop in pressure per time unit exceeds a predetermined threshold value, the membrane is understood to exhibit some defects.
- US-A 4,702,829 describes a process, of the pressurized sealed type, for verifying the integrity of the filters of a hemodiafiltration apparatus, in which the substitu ⁇ tion liquid is realized on-line by passing the dialyzer liquid through two sterile filters arranged one after an- other, each of which exhibits two chambers separated by a water-wettable and semi-permeable membrane, which can hold the germs.
- the verification process of the filter seal begins after the dialysis circuit washing stage, with the circuit full of the detergent liquid and the wa- ter-wettable filter membranes wet.
- the filter seal veri ⁇ fication process uses an ultrafiltration pump, predisposed in the dialysis circuit downstream of the blood treatment device and used in the dialysis treatment for obtaining a patient weight drop measurement.
- the ultrafiltration pump is used to aspirate air internally of the first chamber of the second filter, through a micro- porous water-repelling filter arranged in a breather of the first chamber.
- the aspirated air can also enter the second chamber of the first filter in the absence of occlusions in the circuit branch comprised be ⁇ tween the two filters.
- the liquid that leaves space for the aspirated air is removed by the ultrafiltration pump through the membranes of the two filters.
- the mem ⁇ branes themselves are substantially impermeable to air. Therefore, once the second chamber of the first filter and the first chamber of the second filter are entirely occupied by air at atmospheric pressure, and since the air that has entered the chambers cannot escape through the membrane, the ultrafiltration pump can generate a de ⁇ pression in chambers occupied by the liquid, i.e. the first chamber of the first filter and the second chamber of the second filter. The ultrafiltration pump is then activated until a determined depression has been reached in a part of the dialysis circuit filled with liquid.
- the depression is monitored using a pressure gauge, for example by measuring the time necessary for the pressure to rise by a predetermined quantity, or by measuring the depression after a determined period of time.
- a pressure gauge for example by measuring the time necessary for the pressure to rise by a predetermined quantity, or by measuring the depression after a determined period of time.
- US-A 5,808,181 describes a process for verifying membrane filters arranged in the dialysis circuit of a device for extracorporeal blood treatment, in which the membrane of a filter to be checked is completely wetted with a liq ⁇ uid, a branch of the dialysis circuit containing one of the two filter chambers to be verified is separated from the rest of the circuit, a gas is injected into the sepa ⁇ rated branch to cause an overpressure, while the liquid contained in the chamber is removed by passing through the membrane; the gas supply is interrupted after a pre ⁇ determined overpressure level has been reached in cham ⁇ ber; thereafter, the overpressure is controlled, for ex ⁇ ample by comparing the pressure drop per time unit with a limit value which is characteristic of an intact filter membrane.
- EP-A 0 407 737 describes a process for testing the membrane of a dialyzer filter in two stages: in a first stage the blood chamber of the dialyzer is subjected to a pressure gradient from the blood chamber to the dialyzer fluid chamber; in a second stage the membrane is sub ⁇ jected to an opposite gradient.
- the test enables a deter ⁇ mination of the presence of leaks which might appear or be noted only by effect of one or other of the two pres- sure gradients.
- EP-A 1 898 973 discloses a process for testing filters of treatment fluid of a hemodiafiltration apparatus, wherein each filter has a wet semipermeable membrane which sepa- rates a gas-filled first chamber from a liquid-filled second chamber.
- the first chambers are pressurized by a pump supplying air, while the second chambers are placed in depression by a drainage pump of used dialysis fluid.
- a first closed system is formed which includes the first chambers and a second closed system is formed which in ⁇ cludes the second chambers.
- Two pressure gauges monitor the pressure in the two closed systems for a predeter ⁇ mined time. Summary
- a principal aim of the present invention is to provide a reliable and fast process for the testing of filters com- prising two compartments separated by a porous membrane.
- a further aim of the invention is to provide an apparatus for actuating the process.
- the process of the invention involves establishing a pressure gradient between the compartments of the dry filter, introducing a predefined volume of a testing liquid, e.g. water, into the compartment having the higher pressure, allowing the testing liquid to wet the porous membrane, and subsequently monitoring the pressure gradi- ent between the compartments or measuring gas flow through the membrane .
- a testing liquid e.g. water
- the testing apparatus of the invention comprises means for establishing a pressure gradient between the compart- ments of the filter, means for introducing a predefined quantity of a testing liquid, e.g. water, into the filter and means for monitoring pressure in the filter.
- a testing liquid e.g. water
- Figure 1 is a sectional view of an exemplary embodiment of the testing apparatus of the invention. Detailed Description
- the present invention provides a process for testing a filter comprising two compartments separated by a porous membrane, comprising
- the process of the invention is suitable for testing the integrity of filters comprising two compartments sepa ⁇ rated by a porous membrane.
- filters are membrane filters used in extracorporeal blood treatment, e.g. dialyzers; filters used in the preparation of medi- cal fluids, e.g., pyrogen-free and germ-free fluids like dialysis fluid or substitution fluid; virus filters;
- Each one of the two compartments of the filter generally has at least one fluid inlet or outlet, respectively.
- each of the two compartments has one fluid inlet and one fluid outlet.
- only one of the compartments has both a fluid inlet and a fluid outlet, while the other compartment only has a fluid inlet.
- only one of the compartments has both a fluid inlet and a fluid outlet, while the other compartment only has a fluid outlet.
- only one of the compartments only has a fluid inlet, while the other compartment only has a fluid outlet.
- the dry porous membrane of the filter may take different forms.
- the membrane is a flat sheet membrane or a stack of flat sheet membranes.
- the porous membrane is a hollow fiber mem ⁇ brane or a bundle of hollow fiber membranes.
- the porous membrane may be hydrophilic or hydrophobic, and is comprised of inorganic materials like carbon, glass, ceramics or metals, or organic materials like syn ⁇ thetic polymers.
- suitable synthetic polymers comprise hydrophobic polymers like polysulfones, poly- ethersulfones, polytetrafluoroethylene, polyvinylidene fluoride, polypropylene and hydrophilic polymers like polyvinyl pyrrolidone (PVP) , polyethylene glycol (PEG) , or EVA.
- the testing liquid is a liquid which is able to wet the membrane surface and fill the pores of the membrane.
- Suitable testing liquids are chosen according to the properties of the membrane.
- water, methanol, ethanol or mixtures thereof can be used as testing liquid.
- water is used as testing liquid.
- isopropanol is a suitable testing liquid.
- Other suitable testing liquids for hydrophobic membranes in ⁇ clude liquid hydrocarbons or silicone oils.
- the total pore volume of the membrane is the portion of the membrane volume which is not occupied by solid mate ⁇ rial. It can be calculated by subtracting membrane mass divided by the density of the membrane material from the volume of the membrane (wall) :
- V P V M - (m M / ps ) ,
- V P the total pore volume of the membrane
- V M the volume of the membrane (wall)
- m M the mass of the membrane
- p s the density of the ma ⁇ terial forming the solid portion of the membrane (wall) .
- the volume of testing liquid introduced into the filter is in the range of from P-n-L-n- (d ⁇ ⁇ 20 ⁇ + 400 ⁇ 2 ) to P-n-L-n- (d ⁇ -w + w 2 ) , with n being the number of fibers in the filter, L being the fiber length, P being the porosity of the fiber membrane, d ⁇ being the inner diameter of each fiber, and w being the wall thickness of each fiber.
- n is in the range of from 1,000 to 20,000.
- L is in the range of from 100 to 350 mm.
- P is in the range of from 0.75 to 0.85, i.e. from 75 to 85%.
- d ⁇ is in the range of from 150 to 350 ⁇ .
- w is in the range of from 20 to 50 ⁇ .
- the volume of testing liquid will be in the range of from 5 to 70 ml.
- the filter comprises 1,224 fibers having a length L of 122 mm, an inner diameter d ⁇ of 320 ⁇ , a wall thickness w of 50 ⁇ , and a po ⁇ rosity P of 0.78.
- the filter is tested using 5 ml of water as testing liquid.
- the filter comprises 16,800 fibers having a length L of 250 mm, an inner diameter d ⁇ of 190 ⁇ , a wall thickness w of 40 ⁇ , and a porosity P of 0.82.
- the filter is tested using 60 ml of water as testing liquid .
- the filter comprises 9, 612 fibers having a length L of 236 mm, an inner diameter d ⁇ of 190 ⁇ , a wall thickness w of 35 ⁇ , and a porosity P of 0.80.
- the filter is tested using 30 ml of water as testing liquid .
- steps ii) and iii) are performed by reducing pressure in the filter by connect ⁇ ing one compartment of the filter to a vacuum line or a vacuum pump, and, subsequently or simultaneously, con- necting the other compartment to a testing liquid reservoir containing a predefined volume of testing liquid, so that the testing liquid is sucked into the filter.
- the entire filter is evacuated, all inlets/outlets of the filter are closed and one of the inlets is subsequently connected to a testing liquid reservoir containing a predefined volume of testing liquid.
- one compartment of the filter is connected to a pressurized testing liquid reservoir containing a prede- fined volume of testing liquid, so that the pressure forces the testing liquid into the filter.
- the pressure gradient between the compartments carries the testing liquid into the pores of the membrane, fill- ing the pores at least partially.
- gas perme ⁇ ability of the membrane is substantially reduced and the membrane becomes largely impermeable to gas, if the mem ⁇ brane is intact.
- the process is very fast; transfer of testing liquid into the filter and wetting of the mem- brane is complete within a few seconds.
- the magnitude of the pressure gradient is not critical for the process. It will be chosen to be large enough to be within the measuring range of the equipment used for monitoring the pressure gradient between the compartments of the filter or for measuring gas flow through the membrane, respectively. On the other hand, it will be chosen small enough not to compromise mechanical stability of the membrane or the filter.
- the pressure gradient between the compartments can then be monitored or the gas flow through the membrane can be measured using methods known in the art, for instance with commercially available leak detectors, to verify the integrity of the filter membrane. In comparison to fil ⁇ ters having intact membranes, filters having defective membranes show a faster decrease of the pressure gradient over time between the compartments of the filter, or an increased leak rate.
- a further pressure gra ⁇ washer is established between the compartments of the fil ⁇ ter after the membrane has been wetted, i.e. after step iii) .
- increasing the pressure gradient af- ter the membrane has been wetted may enhance sensitivity or accuracy of the measurement performed in step iv) of the process.
- an overpressure is ap ⁇ plied to one compartment of the filter after the membrane has been wetted, and the increase of pressure in the other compartment over time is monitored. As an alterna ⁇ tive, gas flow through the membrane may be measured.
- an overpressure is ap ⁇ plied to one compartment of the filter through an inlet of the respective compartment after the membrane has been wetted, the inlet is closed and the decrease of pressure in the compartment over time is monitored.
- the orientation of the filter during the test is such that the membrane is in a horizontal position. In another embodiment of the proc ⁇ ess, the orientation of the filter during the test is such that the membrane is in a vertical position. Al ⁇ though the filter can be tested regardless of its orien- tation, for filters comprising a bundle of hollow fiber membranes, it is preferred that the bundle of hollow fi ⁇ ber membranes is in vertical position during the test.
- the predefined amount of testing liquid may be introduced into either compartment of the filter.
- pres ⁇ sure conditions within the filter have to be set accord ⁇ ing to the selection, so that testing liquid is always introduced into the compartment having higher pressure.
- choice of the com ⁇ partment is not expected to have substantial impact on the test.
- the filter comprises an asymmetric membrane, it is generally preferred to introduce the predefined amount of testing liquid into the compartment bordering the selective side of the membrane, i.e. the membrane surface having the smallest pores.
- the predefined amount of testing liquid is introduced into the compartment encom ⁇ passing the lumen of the hollow fiber membranes.
- the present application also provides a device for test- ing a filter comprising two compartments separated by a porous membrane.
- the device comprises
- ii) means for introducing a predefined quantity of
- iii means for monitoring pressure in the filter
- the means for establishing a pressure gradient between the compartments may be a vacuum pump or a vacuum line which is connectable to at least one inlet or outlet of the filter, or a compressor or a pressure line or gas cylinder which is connectable to at least one inlet or outlet of the filter, or a combination thereof.
- the means for introducing a predefined quantity of test ⁇ ing liquid into the filter may be any kind of dispensing device capable of dispensing a predefined quantity of testing liquid. Examples include syringes, injection pumps, and metering pumps, e.g., piston-driven metering pumps .
- the means for introduc ⁇ ing a predefined quantity of testing liquid into the fil- ter comprise a dosage compartment (1) having an inter- ruptible fluid connection (2) to a testing liquid reservoir (3) , an interruptible fluid connection (4) to one of the two compartments of the filter, and a vent pipe (5) comprising a valve.
- a dosage compartment (1) having an inter- ruptible fluid connection (2) to a testing liquid reservoir (3) , an interruptible fluid connection (4) to one of the two compartments of the filter, and a vent pipe (5) comprising a valve.
- the means for introducing a predefined quantity of test ⁇ ing liquid into the filter comprise a dosage compartment (1), a moveable lid (2) between the dosage compartment (1) and a testing liquid reservoir (3), a tube (4) forming the connection to the filter, a vent pipe (5) for venting the dosage compartment (1), a vent pipe (6) for venting the testing liquid reservoir (3) , and an inlet (7) for supplying testing liquid to the testing liquid reservoir (3) .
- Valves in the tube (4) and the vent pipes (5,6) allow for opening and closing the connections.
- the reservoir (3) is filled with testing liquid through inlet (7) while the valve of vent pipe (6) is open. Lid (2) is moved upward while the valves of tube (4) and vent pipe (5) are closed and the testing liquid fills the dosage compartment (1) .
- Lid (2) is lowered to its initial position, sealing the dosage compartment (1) .
- the valves of tube (4) and vent pipe (5) are opened and the testing liquid in dosage compartment (1) is trans- ferred into the filter through tube (4) .
- the dosage com ⁇ partment (1) is interchangeable with dosage compartments holding differing volumes of testing liquid, so that filters having different sizes of membrane surface area may be tested with the device.
- the means for monitoring pressure in the filter or meas ⁇ uring gas flow through the membrane may be any kind of pressure sensors and flow meters that are accurate enough for the device that has to be tested. Examples of such instruments are leak test panels being suitable to detect absolute pressure, difference pressure or mass flow of gas. Such devices are commercially available, for in ⁇ stance, from JW Froehlich GmbH (Leinfelden, Germany) or Zeltwanger Automation GmbH (Dusslingen, Germany) . Suitable examples are devices of the MPS series by JW Froeh- lich, or the DPS-NG series by Zeltwanger Automation GmbH. It will be understood that the features mentioned above and those described hereinafter can be used not only in the combination specified but also in other combinations or on their own, without departing from the scope of the present invention.
- the membrane of the dialyzer consisted of 9612 hollow fi ⁇ bers having an inner diameter of 190 ⁇ and a wall thickness of 35 ⁇ , respectively.
- the fiber length was 260 mm, and the dialyzer provided an effective surface area of 1.35 m 2 on the blood-contacting side.
- the porosity of the membrane was 80%. was used as testing liquid, the volume of water was 30 ml.
- the dialyzer was mounted in a vertical position with the inlet of the blood compartment being directed downwards.
- the inlet of the blood compartment was connected to the metering device shown in figure 1.
- the outlet of the blood compartment on the opposite side of the dialyzer was closed.
- the inlet of the dialysate compartment was connected to a vacuum source, the dialyzer being sepa ⁇ rated from the vacuum source by a valve.
- the outlet of the dialysate compartment was closed.
- the dosage compartment (1) of the metering device is de ⁇ signed to provide a total volume of 30 ml.
- the reservoir (3) was filled with water through the inlet (7) while the valve of the vent pipe (6) was open.
- the lid (2) was moved upwards while the valves of the tube (4) , which had a diameter of 4 mm and a length of 274 mm, and the vent pipe (5) were closed, and the water filled the dosage compartment (1) .
- the lid (2) was lowered to its initial position sealing the dosage compartment (1) .
- vacuum was applied to the dialyzer by opening the valve between the vacuum pump and the dialyzer.
- the vacuum source was separated from the dialyzer by closing the valve between the vacuum pump and the dialyzer.
- the valves of tube (4) and the vent pipe (5) at the metering device were opened and the water inside the dosage compartment (1) was transferred into the filter through tube (4) by the air stream entering the dosage compartment (1) through the vent pipe (5) .
- the water was distributed homogeneously inside the blood compartment, wetting the inner surface of all hollow fiber membranes and thus reducing gas permeability of the porous struc ⁇ ture .
- a leak test panel (Type: MPS200, JW Froehlich GmbH) was connected to the outlet of the blood compartment of the dialyzer.
- the inlet of the blood com ⁇ partment remained closed and both ports of the dialysate compartment were opened to atmospheric pressure.
- a pressure of 1.6 bar was applied to the blood compart ⁇ ment of the dialyzer for 2.5 seconds, and the ports of the blood compartment were closed. After a leveling phase of one second, pressure decrease inside the blood com ⁇ partment was measured for another second before the sys ⁇ tem was vented for 1.5 seconds.
- the absolute pressure de ⁇ crease within the measuring phase of one second is an in- dicator of membrane integrity. Including filling and venting, the total time required for this test was six seconds .
- 35 pieces of dry dialyzers were processed as described above, 25 pieces having intact membranes and 10 pieces having defective membranes.
- a mean pressure decrease of 20.1 mbar on the blood contacting side was observed within the measuring phase of one second in case of the 25 dialyzers having intact membranes.
- the standard devia- tion of the 25 values measured on these dialyzers was de ⁇ termined to be 0.7 mbar, with the lowest value being 18.7 mbar and the highest value being 21.4 mbar.
- the 10 pieces of dialyzers having defective membranes showed a significantly increased pressure drop in the range of from 30.0 mbar up to 62.4 mbar .
- the minimum amount of water required to reliably wet the membrane can be calculated using the equation P-n-L-n- (d ⁇ ⁇ 20 ⁇ + 400 ⁇ 2 ) with n being the number of fibers in the filter, L being the fiber length, P being the porosity of the fiber membrane, d ⁇ being the inner diameter of each fiber, and w being the wall thickness of each fiber.
- the minimum amount is calcu ⁇ lated to be 26.4 ml.
- a pressure of 1.6 bar was applied to the blood compart- ment of the dialyzer for 2.5 seconds and the ports of the blood compartment were closed. After a leveling phase of one second, pressure decrease inside the blood compart ⁇ ment was measured for another 10 seconds. Finally, the system was vented for 1.5 seconds.
- the eight filters showed a mean pressure decrease during the measuring phase of 195 mbar with the minimum value being 187 mbar and the maximum value being 202 mbar. All eight dialyzers were dried afterwards by applying an airstream of 4 m 3 h -1 through the blood compartment for one hour. After drying of the filters, the experiment was repeated using 27 ml of water instead of 30 ml.
- the eight filters this time showed a mean pressure decrease during the measuring phase of 230 mbar with the minimum value being 223 mbar and the maximum value being 239 mbar.
- the reduced amount of water used to wet the membrane resulted in an increased gas permeabil ⁇ ity of the membrane.
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- Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Analytical Chemistry (AREA)
- Physics & Mathematics (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Dispersion Chemistry (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Immunology (AREA)
- Pathology (AREA)
- Separation Using Semi-Permeable Membranes (AREA)
- External Artificial Organs (AREA)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP11741239.5A EP2603309B1 (de) | 2010-08-11 | 2011-08-10 | Verfahren zum testen von hohlfasermembranfiltern |
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP10172450A EP2418012A1 (de) | 2010-08-11 | 2010-08-11 | Vorrichtung und Verfahren zum Testen von Filtern |
EP11741239.5A EP2603309B1 (de) | 2010-08-11 | 2011-08-10 | Verfahren zum testen von hohlfasermembranfiltern |
PCT/EP2011/063756 WO2012020048A1 (en) | 2010-08-11 | 2011-08-10 | Device and process for testing hollow fibre membrane filters |
Publications (2)
Publication Number | Publication Date |
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EP2603309A1 true EP2603309A1 (de) | 2013-06-19 |
EP2603309B1 EP2603309B1 (de) | 2014-03-26 |
Family
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EP10172450A Withdrawn EP2418012A1 (de) | 2010-08-11 | 2010-08-11 | Vorrichtung und Verfahren zum Testen von Filtern |
EP11741239.5A Active EP2603309B1 (de) | 2010-08-11 | 2011-08-10 | Verfahren zum testen von hohlfasermembranfiltern |
Family Applications Before (1)
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EP10172450A Withdrawn EP2418012A1 (de) | 2010-08-11 | 2010-08-11 | Vorrichtung und Verfahren zum Testen von Filtern |
Country Status (5)
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US (1) | US9243991B2 (de) |
EP (2) | EP2418012A1 (de) |
JP (1) | JP5891225B2 (de) |
CN (1) | CN103025409B (de) |
WO (1) | WO2012020048A1 (de) |
Families Citing this family (15)
Publication number | Priority date | Publication date | Assignee | Title |
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GB2503162B (en) | 2011-03-23 | 2018-08-22 | Nxstage Medical Inc | Peritoneal dialysis systems and devices |
US9861733B2 (en) | 2012-03-23 | 2018-01-09 | Nxstage Medical Inc. | Peritoneal dialysis systems, devices, and methods |
JP2014128780A (ja) * | 2012-12-27 | 2014-07-10 | Nihon Medi Physics Co Ltd | フィルター完全性試験機構を備えた薬液分注機 |
DE102015120003A1 (de) | 2015-11-18 | 2017-06-01 | B. Braun Avitum Ag | Verfahren zur Sterilisation und Integritätsprüfung von Dialysatoren |
DE102016012722A1 (de) | 2016-10-24 | 2018-04-26 | Fresenius Medical Care Deutschland Gmbh | Verfahren zur Bestimmung einer Permeationseigenschaft von Hohlfasermembranen |
DE102016012730A1 (de) * | 2016-10-24 | 2018-04-26 | Fresenius Medical Care Deutschland Gmbh | Verfahren zur Bestimmung einer Permeationseigenschaft von Hohlfasermembranen |
EP3641850B1 (de) | 2017-06-24 | 2024-10-09 | NxStage Medical Inc. | Systeme zur herstellung von peritonealdialyseflüssigkeit |
CN107290252B (zh) * | 2017-06-30 | 2019-10-11 | 浙江石金玄武岩纤维股份有限公司 | 一种测试纤维浸润性能的方法 |
EP3444022A1 (de) * | 2017-08-16 | 2019-02-20 | Gambro Lundia AB | Verfahren zum testen von filtern |
US11872337B2 (en) | 2018-02-28 | 2024-01-16 | Nxstage Medical, Inc. | Fluid preparation and treatment devices methods and systems |
EP3560577A1 (de) | 2018-04-25 | 2019-10-30 | Gambro Lundia AB | Vorrichtung und verfahren zur integritätsprüfung einer ultrafiltermembran |
CN110879195B (zh) * | 2018-09-05 | 2021-11-12 | 宁波方太厨具有限公司 | 一种分辨滤芯内芯的检测方法 |
KR102342446B1 (ko) * | 2018-10-18 | 2021-12-22 | 주식회사 엘지화학 | 분리막 엘리먼트의 결함 검출 방법 및 분리막 엘리먼트 결함 검출 장치 |
CN111013395A (zh) * | 2020-03-01 | 2020-04-17 | 贝士德仪器科技(北京)有限公司 | 滤膜前端控压方法及滤膜孔径测试装置 |
CN112808015A (zh) * | 2020-12-25 | 2021-05-18 | 德蓝水技术股份有限公司 | 一种中空纤维膜的检测方法及装置 |
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GB2132366B (en) | 1982-12-27 | 1987-04-08 | Brunswick Corp | Method and device for testing the permeability of membrane filters |
DE3477691D1 (en) | 1983-09-09 | 1989-05-18 | Fujisawa Pharmaceutical Co | Apparatus for testing membrane filters, and apparatus for sterilizing liquids with use of membrane filter |
DE3444671A1 (de) | 1984-12-07 | 1986-06-12 | Fresenius AG, 6380 Bad Homburg | Haemodiafiltrationsgeraet |
DE3923078C1 (de) | 1989-07-13 | 1990-09-27 | Fresenius Ag, 6380 Bad Homburg, De | |
JPH0523551A (ja) * | 1991-07-18 | 1993-02-02 | Fuji Photo Film Co Ltd | 完全性試験装置 |
DE4209519C3 (de) | 1992-03-24 | 2000-06-15 | Pall Corp | Verfahren und Gerät zum schnellen Testen der Unversehrtheit von Filterelementen |
DE69313574T2 (de) * | 1992-05-01 | 1998-01-08 | Filtec Corp | Vorrichtung zur Integritätsprüfung von Membranfiltern |
US5507959A (en) * | 1994-11-04 | 1996-04-16 | Advanced Micro Devices, Inc. | Apparatus for wetting, flushing and performing integrity checks on encapsulated PTFE filters |
DE19534417A1 (de) | 1995-09-16 | 1997-03-20 | Fresenius Ag | Verfahren zum Überprüfen von mindestens einem im Dialysierflüssigkeitssystem einer Vorrichtung zur extrakorporalen Blutbehandlung angeordneten Filter |
FR2749190B1 (fr) | 1996-05-28 | 1998-09-18 | Omnium Traitement Valorisa | Procede et installation pour tester in situ l'integrite des membranes de filtration |
JP3401139B2 (ja) * | 1996-07-02 | 2003-04-28 | テルモ株式会社 | 中空繊維膜モジュールのリーク試験方法及び試験装置 |
US5786528A (en) * | 1996-09-10 | 1998-07-28 | Millipore Corporation | Water intrusion test for filters |
JP2002537105A (ja) * | 1999-02-26 | 2002-11-05 | ユナイテッド・ステイツ・フィルター・コーポレイション | 膜を評価する方法及び装置 |
JP2001242066A (ja) * | 2000-03-01 | 2001-09-07 | Toyobo Co Ltd | 非対称構造を有する多孔質膜のリークテスト法 |
FR2828116B1 (fr) * | 2001-08-06 | 2003-11-14 | Ondeo Degremont | Procede et dispositif de controle de l'integrite des modules de filtration membranaire |
JP2004167384A (ja) * | 2002-11-20 | 2004-06-17 | Toray Ind Inc | 中空糸膜のリークテスト法 |
CN1255683C (zh) * | 2003-07-09 | 2006-05-10 | 天津泰达新水源科技开发有限公司 | 中空纤维分离膜的自动在线检测装置 |
US20050229679A1 (en) * | 2004-04-16 | 2005-10-20 | Porous Materials, Inc. | Automated clamp-on sample chamber for flow porometry and a method of using same |
EP1710011A1 (de) * | 2005-04-07 | 2006-10-11 | Gambro Lundia AB | Filtrationsmembrane |
WO2007003980A1 (en) | 2005-07-01 | 2007-01-11 | Gambro Lundia Ab | An apparatus and process for testing filters |
FR2894843B1 (fr) * | 2005-12-20 | 2008-02-22 | Degremont Sa | Procede et dispositif de test d'integrite de membranes de filtration |
-
2010
- 2010-08-11 EP EP10172450A patent/EP2418012A1/de not_active Withdrawn
-
2011
- 2011-08-10 JP JP2013523606A patent/JP5891225B2/ja active Active
- 2011-08-10 CN CN201180036168.2A patent/CN103025409B/zh active Active
- 2011-08-10 EP EP11741239.5A patent/EP2603309B1/de active Active
- 2011-08-10 WO PCT/EP2011/063756 patent/WO2012020048A1/en active Application Filing
- 2011-08-10 US US13/814,125 patent/US9243991B2/en active Active
Non-Patent Citations (1)
Title |
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See references of WO2012020048A1 * |
Also Published As
Publication number | Publication date |
---|---|
CN103025409A (zh) | 2013-04-03 |
EP2418012A1 (de) | 2012-02-15 |
US20130205873A1 (en) | 2013-08-15 |
JP5891225B2 (ja) | 2016-03-22 |
EP2603309B1 (de) | 2014-03-26 |
WO2012020048A1 (en) | 2012-02-16 |
US9243991B2 (en) | 2016-01-26 |
JP2013535328A (ja) | 2013-09-12 |
CN103025409B (zh) | 2015-11-25 |
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